The primary aims of this study are to determine how many patients become sensitized (develop a Th1 immune response) to brain antigens after stroke and whether infection in the immediate post-stroke period increases the risk of becoming sensitized to those antigens. The rationale for this study is based on the fact that the integrity of the blood-brain barrier is breached in stroke; cells of the immune system thus encounter novel central nervous system (CMS) antigens in both the brain and in the systemic circulation. This encounter may result in an immune response to those antigens and the microenvironment at the site of encounter determines the nature of the immune response generated. For instance, a systemic inflammatory response, such as occurs with infection, could induce the expression of costimulatory molecules and promote sensitization of lymphocytes (Th1 immune response) to brain antigens. In animal models of stroke, lymphocytes sensitized to CMS antigens contribute to cerebral injury and manipulation of the immune response improves outcome from stroke. Similar manipulation of the immune response could provide a therapeutic target for clinical intervention. To date, however, attempts at manipulating the immune response in patients with stroke have produced either no clinical benefit or even harm. Thus, prior to conducting further trials of immune modulation in clinical stroke, the nature and the consequences of the post-ischemic immune response need to be understood. For the purposes of this study, antigen-specific immune responses to brain antigens will be evaluated serially over the course of 1 year in patients who present with acute ischemic stroke; the type of immune response, Th1 versus Th2/Th3, will be compared between patients who develop infection in the immediate post-stroke period and those who do not. The effect of stroke subtype and endogenous immunomodulatory responses on the likelihood of becoming sensitized to brain antigens will also be assessed. Progression of white matter disease and brain atrophy, as detected by magnetic resonance imaging, will be used as a surrogate measure of the pathologic consequences of a Th1 response. Data derived from this study will be used to plan future trials of immunomodulation in patients with stroke.
| Zierath, Dannielle; Tanzi, Patricia; Shibata, Dean et al. (2018) Cortisol is More Important than Metanephrines in Driving Changes in Leukocyte Counts after Stroke. J Stroke Cerebrovasc Dis 27:555-562 |
| Becker, Kyra J; Tanzi, Patricia; Zierath, Dannielle et al. (2016) Antibodies to myelin basic protein are associated with cognitive decline after stroke. J Neuroimmunol 295-296:9-11 |
| Becker, Kyra J (2016) Inflammation and the Silent Sequelae of Stroke. Neurotherapeutics 13:801-810 |
| Becker, Kyra; Kohen, Ruth; Lee, Richard et al. (2015) Poststroke fatigue: hints to a biological mechanism. J Stroke Cerebrovasc Dis 24:618-21 |
| Becker, Kyra J; Dankwa, Dorender; Lee, Richard et al. (2014) Stroke, IL-1ra, IL1RN, infection and outcome. Neurocrit Care 21:140-6 |
| Weinstein, Jonathan R; Schulze, Juliane; Lee, Richard V et al. (2014) Functional polymorphisms in toll-like receptor 4 are associated with worse outcome in acute ischemic stroke patients. Neuroreport 25:580-4 |
| Kunze, Allison; Zierath, Dannielle; Tanzi, Patricia et al. (2014) Peroxiredoxin 5 (PRX5) is correlated inversely to systemic markers of inflammation in acute stroke. Stroke 45:608-10 |
| Schulze, Juliane; Zierath, Dannielle; Tanzi, Patricia et al. (2013) Severe stroke induces long-lasting alterations of high-mobility group box 1. Stroke 44:246-8 |
| Becker, Kyra; Tanzi, Pat; Kalil, Angela et al. (2013) Early statin use is associated with increased risk of infection after stroke. J Stroke Cerebrovasc Dis 22:66-71 |
| Becker, Kyra (2012) Autoimmune responses to brain following stroke. Transl Stroke Res 3:310-7 |
Showing the most recent 10 out of 19 publications
